Effects of nifedipine and nickel on plateau potentials generated in submucosal interstitial cells distributed in the mouse proximal colon.

The effects of nifedipine and nickel ions (Ni2+), known inhibitors of L- and T-type voltage-gated Ca-channels respectively, were investigated on plateau potentials recorded from submucosal interstitial cells distributed in the mouse proximal colon. Plateau potentials were generated at a frequency of about 15 times min(-1) and were formed of two components. The primary component had an initial fast rate of rise with a transient potential (rate of rise, 130 mV/s; peak amplitude, 35 mV) and was followed by a secondary plateau component with a sustained potential (amplitude, 25 mV; duration, 2.6 s). Each cell from which recordings were made was injected with neurobiotin. Subsequent morphological examination with a confocal microscope indicated successful visualization of injected cells only in the presence of 18beta-glycylrhetinic acid (an inhibitor of gap junctional connections), suggesting that these cells were dye-coupled with surrounding cells. The cells injected with neurobiotin exhibited an oval-shaped cell body with bipolar processes and were distributed in the submucosal layer, suggesting that they were submucosal interstitial cells of Cajal (ICC-SM). The plateau potentials were not altered by 0.01 microM nifedipine, but were reduced in duration by 0.1 microM nifedipine, and abolished by 1 microM nifedipine. The rate of rise of plateau potentials, but not their amplitude, was reduced by Ni2+ (> 10 microM), with no significant alteration of the membrane potential. In the presence of 100 microM Ni2+, the plateau potentials were changed to a triangular form. Thus, the plateau potentials were formed by two types of voltage-gated channel current: the initial component was produced by a Ni2+-sensitive channel current and the plateau component by a nifedipine-sensitive current. The possible involvement of two different types of voltage-gated Ca2+-channels in the generation of submucosal pacemaker potentials was discussed.